|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 2 December 2004
doi: 10.1242/dev.01571
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Program in Developmental Biology, The Research Institute, Hospital for Sick
Children, Toronto, Ontario M5G 1X8, Canada
2 Program in Genetics, The Research Institute, Hospital for Sick Children,
Toronto, Ontario M5G 1X8, Canada
3 Department of Molecular and Medical Genetics, University of Toronto, Toronto,
Ontario, Canada
4 Laboratory of Developmental Neurogenetics, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892,
USA
5 MRC Human Genetics Unit, Western General Hospital, Crewe Road South, Edinburgh
EH4 2XU, UK
6 Ottawa Health Research Institute, Ottawa, Ontario K1H 8L6, Canada
7 Department of Cellular and Molecular Medicine, and University of Ottawa Center
for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario K1H 8M5,
Canada
8 Department of Pediatrics, University of Toronto, Toronto, Ontario,
Canada
Author for correspondence (e-mail:
mcinnes{at}sickkids.ca)
Accepted 2 November 2004
During vertebrate eye development, the cells of the optic vesicle (OV) become either neuroretinal progenitors expressing the transcription factor Chx10, or retinal pigment epithelium (RPE) progenitors expressing the transcription factor Mitf. Chx10 mutations lead to microphthalmia and impaired neuroretinal proliferation. Mitf mutants have a dorsal RPE-to-neuroretinal phenotypic transformation, indicating that Mitf is a determinant of RPE identity. We report here that Mitf is expressed ectopically in the Chx10or-J/or-J neuroretina (NR), demonstrating that Chx10 normally represses the neuroretinal expression of Mitf. The ectopic expression of Mitf in the Chx10or-J/or-J NR deflects it towards an RPE-like identity; this phenotype results not from a failure of neuroretinal specification, but from a partial loss of neuroretinal maintenance. Using Chx10 and Mitf transgenic and mutant mice, we have identified an antagonistic interaction between Chx10 and Mitf in regulating retinal cell identity. FGF (fibroblast growth factor) exposure in a developing OV has also been shown to repress Mitf expression. We demonstrate that the repression of Mitf by FGF is Chx10 dependent, indicating that FGF, Chx10 and Mitf are components of a pathway that determines and maintains the identity of the NR.
Key words: Mouse, Mitf, Chx10, FGF, RPE, Neuroretina
This article has been cited by other articles:
|
|
 |
|
  T. Wataya, S. Ando, K. Muguruma, H. Ikeda, K. Watanabe, M. Eiraku, M. Kawada, J. Takahashi, N. Hashimoto, and Y. Sasai Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation PNAS, August 19, 2008; 105(33): 11796 - 11801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bharti, W. Liu, T. Csermely, S. Bertuzzi, and H. Arnheiter Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF Development, March 15, 2008; 135(6): 1169 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Muller, H. Rohrer, and A. Vogel-Hopker Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo Development, October 1, 2007; 134(19): 3483 - 3493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xu, P. D. Witmer, S. Lumayag, B. Kovacs, and D. Valle MicroRNA (miRNA) Transcriptome of Mouse Retina and Identification of a Sensory Organ-specific miRNA Cluster J. Biol. Chem., August 24, 2007; 282(34): 25053 - 25066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Karali, I. Peluso, V. Marigo, and S. Banfi Identification and Characterization of MicroRNAs Expressed in the Mouse Eye Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 509 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Esumi, S. Kachi, P. A. Campochiaro, and D. J. Zack VMD2 Promoter Requires Two Proximal E-box Sites for Its Activity in Vivo and Is Regulated by the MITF-TFE Family J. Biol. Chem., January 19, 2007; 282(3): 1838 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Cho and C. L. Cepko Wnt2b/{beta}-catenin-mediated canonical Wnt signaling determines the peripheral fates of the chick eye Development, August 15, 2006; 133(16): 3167 - 3177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Morcillo, J. R. Martinez-Morales, F. Trousse, Y. Fermin, J. C. Sowden, and P. Bovolenta Proper patterning of the optic fissure requires the sequential activity of BMP7 and SHH Development, August 15, 2006; 133(16): 3179 - 3190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Livne-bar, M. Pacal, M. C. Cheung, M. Hankin, J. Trogadis, D. Chen, K. M. Dorval, and R. Bremner Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina PNAS, March 28, 2006; 103(13): 4988 - 4993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Goding and F. L. Meyskens Jr. Microphthalmic-Associated Transcription Factor Integrates Melanocyte Biology and Melanoma Progression Clin. Cancer Res., February 15, 2006; 12(4): 1069 - 1073. [Full Text] [PDF]
|
|
|
|
|
|
K. M. Dorval, B. P. Bobechko, H. Fujieda, S. Chen, D. J. Zack, and R. Bremner CHX10 Targets a Subset of Photoreceptor Genes J. Biol. Chem., January 13, 2006; 281(2): 744 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Dhomen, K. S. Balaggan, R. A. Pearson, J. W. Bainbridge, E. M. Levine, R. R. Ali, and J. C. Sowden Absence of Chx10 Causes Neural Progenitors to Persist in the Adult Retina Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 386 - 396. [Abstract] [Full Text] [PDF]
|
|
